In-Source Photoderivatization-Enhanced Neurometabolic Profiling Deciphers Vascular Cognitive Impairment

Area of Science:

• Neuroscience
• Analytical Chemistry
• Biochemistry

Background:

• Vascular cognitive impairment (VCI) pathogenesis is poorly understood due to challenges in neurometabolic profiling.
• Detecting low-abundance metabolites and neurotransmitters (NTs) is difficult with current high-throughput methods.

Purpose of the Study:

• To develop a novel mass spectrometry in-source photoderivatization (MSIPD) platform for enhanced neurometabolic profiling.
• To improve the detection of neurotransmitters in VCI research.

Main Methods:

• Utilized a novel photoreactive probe (5-methoxy-2-nitrobenzaldehyde) and TiO2 P25 for MSIPD.
• Employed laser desorption/ionization mass spectrometry (LDI-MS) for rapid, low-sample-volume analysis.
• Analyzed cerebrospinal fluid (CSF) from VCI patients and controls.

Main Results:

• Achieved over 93% derivatization efficiency and high reproducibility (≤8.2%) for NTs.
• Increased metabolite coverage twofold compared to underivatized samples.
• Identified 12 significantly altered neuro-metabolites in VCI patients and stage-dependent changes in NTs like histamine and phenylalanine.

Conclusions:

• Neurometabolic dysregulation, particularly of NTs, is implicated in VCI pathogenesis.
• The MSIPD platform offers a sensitive, rapid, and efficient tool for translational neurometabolic profiling.
• Findings provide insights into VCI progression and potential therapeutic targets.